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Title of article :
Design and biological evaluation of phenyl-substituted analogs of β-phenylethylidenehydrazine Original Research Article
Author/Authors :
Bernard Sowa، نويسنده , , Gillian Rauw، نويسنده , , Asghar Davood، نويسنده , , Afshin Fassihi، نويسنده , , Edward E. Knaus، نويسنده , , Glen B. Baker، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2005
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Abstract :
β-Phenylethylidenehydrazine (PEH) has been demonstrated previously to be an inhibitor of γ-aminobutyric acid transaminase (GABA-T) and to cause a marked increase in rat brain levels of GABA, a major neurotransmitter. A group of PEH analogs, possessing a variety of substituents (Me, OMe, Cl, F, and CF3) at the 2-, 3-, and 4-positions of the phenyl ring, were synthesized for evaluation as inhibitors of GABA-T. The details of the synthesis and chemical characterization of the analogs are described. Preliminary in vitro screening for GABA-T inhibition showed that all the analogs possessed activity against this enzyme, although substitution of CF3 at the 2- and 4-positions caused reduced activity. One of the drugs, 4-fluoro-β-phenylethylidenehydrazine, was investigated further ex vivo, where it was shown to inhibit GABA-T, elevate brain levels of GABA, and decrease levels of glutamine, similar to the profile observed previously for PEH.
Keywords :
Glutamine , GABA transaminase , ?-Aminobutyric acid , ?-Phenylethylidenehydrazine
Journal title :
Bioorganic and Medicinal Chemistry
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